Poster Presentation Epigenetics 2013

Structural and Functional Characterization of Epigenetic Regulator Smchd1 (#232)

Kelan Chen 1 , James M Murphy 1 , Marnie E Blewitt 1
  1. Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia

Epigenetic regulation of gene expression is fundamental in controlling biological processes in multicellular organisms. Structural maintenance of chromosome hinge domain containing 1 (Smchd1) was initially identified as an epigenetic repressor that is critical for X chromosome inactivation in female mice. Recent studies have demonstrated that Smchd1 also regulates a subset of autosomal genes that are subject to monoallelic expression. Smchd1 also behaves as a tumour suppressor in mice and is implicated in facioscapulohumeral muscular dystrophy (FSHD) in human. However, it is still unclear how Smchd1 functions at molecular level. This study aims to characterize the structure and function of Smchd1 protein, mainly focusing on its DNA interacting Hinge domain and putative GHKL ATPase domain. By using a combination of biochemical and structural approaches, we are investigating Smchd1’s DNA and ATP binding activity and determining its protein structure. Together with our preliminary results from chromatin immunoprecipitation experiment and protein-protein interaction analysis, we are providing insight into how this protein acts as an epigenetic regulator.